Dr. Gr neberg began by outlining changing trends in antimicrobial susceptibility around the world. Data from the Alexander Project demonstrate that there is a huge global variation in prevalence of penicillin-resistant Streptococcus pneumoniae (or PRSP). Hong Kong has a staggering 73.8% high-level penicillin resistance rate while the corresponding rate in Brazil is only 1.3%. In the US, 12.9% of S. pneumoniae show intermediate-level penicillin resistance, and 28.1% possess high-level resistance.

The situation also fluctuates widely throughout Europe, with the lowest rate of high-level PRSP reported in the Czech Republic at 2.0%, compared to 7.8% in the UK and 45.3% in France.

A range in the incidence of macrolide-resistant S. pneumoniae (or MRSP) around the world has also been identified, from a high of 82.2% in Hong Kong, to 21.5% in Mexico and 0.5% in Kenya.

Throughout Europe, a wide variation exists in the incidence of MRSP, from a high of 57.1% in Spain to 8.8% in Switzerland and a low of 2.0% in the Czech Republic. It is imperative for physicians to be aware of this wide variation across geographical regions, and of the resistance patterns in their own locale, in order to prescribe effective empiric therapy.

The importance of assessing resistance rates is highlighted by data showing that cross resistance between macrolides and penicillin is commonly seen in S. pneumoniae, with 16.0% of S. pneumoniae isolates worldwide reported to be both erythromycin and penicillin resistant.

In sharp contrast, it has been demonstrated that S. pneumoniae possesses almost no cross-resistance between penicillin and levofloxacin.

In fact, the majority of countries tested found no fluoroquinolone resistance at all. In five of the seven countries reporting fluoroquinolone resistance, the rates were very low, ranging from 1-2%. Two countries with higher levels of resistance were South Korea and Hong Kong. However, Dr. Gr neberg commented that the situation in Hong Kong was very different from that of the rest of the world, and in general, pneumococci remain exquisitely sensitive to levofloxacin. Notably, a separate surveillance study conducted in Canada in 1988 and from 1993 to 1998 found an increase in the prevalence of pneumococci with reduced susceptibility to one of the fluoroquinolones, namely ciprofloxacin.

Dr. Gr neberg also compared the anti-pneumococcal activity of levofloxacin with b-lactams. According to the National Committee for Clinical Laboratory Standards for percent susceptibility, levofloxacin possessed the highest activity rate with 98.4% of S. pneumoniae isolates fully susceptible to levofloxacin. In contrast, 63.6% were sensitive to either penicillin or cefixime, and only 59.5% were sensitive to cefaclor.

In addition, only 68% of S. pneumoniae isolates were susceptible to clarithromycin, azithromycin, or erythromycin. The meaning of this clinically depends on whether one is dealing with high-level (target change) resistance or low-level (efflux) macrolide resistance.

Analysis of the 1999-2000 PROTEKT isolates revealed that almost all strains of Moraxella catarrhalis produce b-lactamase, and approximately 10-15% of Haemophilus influenzae worldwide are b-lactamase producers. The Alexander Project data show that the incidence of b-lactamase production among H. influenzae is 28.7% in the United States, 12.3% in Europe, 13.5% in Kenya and 24.0% in Singapore.

Dr. Gr neberg noted that penicillin and macrolide resistance in S. pneumoniae continues to evolve worldwide, with particularly high prevalence levels in the Far East. In addition, b-lactamase production occurs in a notable proportion of isolates of H. influenzae in many countries and the prevalence of b-lactamase production among isolates of M. catarrhalis is very high in all countries studied.

In marked contrast to this, although recognized among isolates in certain geographical regions, resistance to fluoroquinolones occurs infrequently worldwide. With antimicrobial resistance varying from country to country, it is important to consider local resistance patterns when prescribing antimicrobials.

Irrespective of penicillin or macrolide resistance, certain fluoroquinolones possess excellent activity against isolates of S. pneumoniae, the most important respiratory pathogen. Fluoroquinolones are also highly active against other respiratory tract pathogens, with levofloxacin showing 100% activity against b-lactamase producing strains of Haemophilus spp., M. catarrhalis and Streptococcus pyogenes. Dr. Gr neberg concluded that continued vigilance is necessary to maintain the excellent efficacy of these agents.